Interleukin-1 stimulates catabolism in C2C12 myotubes
AUTOR(ES)
Li, Wei
FONTE
American Physiological Society
RESUMO
Interleukin-1 (IL-1) is an inflammatory cytokine that has been linked to muscle catabolism, a process regulated by muscle-specific E3 proteins of the ubiquitin-proteasome pathway. To address cellular mechanism, we tested the hypothesis that IL-1 induces myofibrillar protein loss by acting directly on muscle to increase expression of two critical E3 proteins, atrogin1/muscle atrophy F-box (MAFbx) and muscle RING-finger 1 (MuRF1). Experiments were conducted using mature C2C12 myotubes to eliminate systemic cytokine effects and avoid paracrine signaling by nonmuscle cell types. Time-course protocols were used to define the sequence of cellular responses. We found that atrogin1/MAFbx mRNA and MuRF1 mRNA are elevated 60–120 min after myotube exposure to either IL-1α or IL-1β. These responses are preceded by signaling events that promote E3 expression. Both IL-1 isoforms stimulate phosphorylation of p38 mitogen-activated protein kinase and stimulate nuclear factor-κB (NF-κB) signaling; I-κB levels fall and NF-κB DNA binding activity increases. Other regulators of E3 expression are unaffected by IL-1 [cytosolic oxidant activity, Forkhead-O (Foxo) activity] or respond paradoxically (AKT). Chronic exposure of C2C12 myotubes over 48 h resulted in reduced myotube width and loss of sarcomeric actin. We conclude that IL-1α and IL-1β act via an oxidant- and AKT/Foxo-independent mechanism to activate p38 MAPK, stimulate NF-κB signaling, increase expression of atrogin1/MAFbx and MuRF1, and reduce myofibrillar protein in differentiated myotubes.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2740393Documentos Relacionados
- Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity[S]
- Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition
- Differentiation and long-term survival of C2C12 myoblast grafts in heart.
- ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation.
- Borrelia burgdorferi stimulates release of interleukin-1 activity from bovine peripheral blood monocytes.